A defined Oct4 level governs cell state transitions of pluripotency entry and differentiation into all embryonic lineages

Aliaksandra Radzisheuskaya, Gloryn Le Bin Chia, Rodrigo L. Dos Santos, Thorold W. Theunissen, L. Filipe C. Castro, Jennifer Nichols, José C.R. Silva

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Oct4 is considered a master transcription factor for pluripotent cell self-renewal, but its biology remains poorly understood. Here, we investigated the role of Oct4 using the process of induced pluripotency. We found that a defined embryonic stem cell (ESC) level of Oct4 is required for pluripotency entry. However, once pluripotency is established, the Oct4 level can be decreased up to sevenfold without loss of self-renewal. Unexpectedly, cells constitutively expressing Oct4 at an ESC level robustly differentiated into all embryonic lineages and germline. In contrast, cells with low Oct4 levels were deficient in differentiation, exhibiting expression of naive pluripotency genes in the absence of pluripotency culture requisites. The restoration of Oct4 expression to an ESC level rescued the ability of these to restrict naive pluripotent gene expression and to differentiate. In conclusion, a defined Oct4 level controls the establishment of naive pluripotency as well as commitment to all embryonic lineages.

Original languageEnglish
Pages (from-to)579-590
Number of pages12
JournalNature Cell Biology
Volume15
Issue number6
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Fingerprint Dive into the research topics of 'A defined Oct4 level governs cell state transitions of pluripotency entry and differentiation into all embryonic lineages'. Together they form a unique fingerprint.

  • Cite this

    Radzisheuskaya, A., Le Bin Chia, G., Dos Santos, R. L., Theunissen, T. W., Castro, L. F. C., Nichols, J., & Silva, J. C. R. (2013). A defined Oct4 level governs cell state transitions of pluripotency entry and differentiation into all embryonic lineages. Nature Cell Biology, 15(6), 579-590. https://doi.org/10.1038/ncb2742